It is proposed to investigate three major areas related to melanocyte-stimulating hormone (MSH) and the hormone which controls its release. Previous work on this project has established the inhibitory influence of a substance present in hypothalamic tissue upon release of MSH from the pituitary. The chemical structure of this substance or substances remains to be clarified. First, it is proposed to determine the identity of this MSH-release inhibiting factor (MIF) as well as releasers of MSH from the pituitary and characterize the dynamics involved in the release. Secondly, the extra-pigmentary effects of MSH upon the central nervous system will be investigated. In particular, several behavioral effects will be studied in an attempt to determine the functional role of MSH in mammals. Thirdly, it appears from work done previously on this project that a substance found in the hypothalamus with MIF activity has direct effects upon the brain which do not require the presence of the pituitary gland. This MIF tripeptide, Pro-Leu-Gly-NH2, is active in several systems which some investigators consider animal models of parkinsonism and mental depression. It is proposed to continue these investigations and determine the mechanism by which these effects are exerted upon the central nervous system.